%0 Journal Article
%T Extracellular vesicle-associated A¦Â mediates trans-neuronal bioenergetic and Ca2+-handling deficits in Alzheimer¡¯s disease models
%A Caitlin Suire
%A Chinmoyee Maharana
%A Dimitrios Kapogiannis
%A Dong Liu
%A Emmette R Hutchison
%A Erez Eitan
%A Gregory A Jicha
%A James Comotto
%A Kenneth W Witwer
%A Krisztina Marosi
%A Maja Mustapic
%A Mark P Mattson
%A Saket M Nigam
%A Vasiliki Machairaki
%J Archive of "NPJ Aging and Mechanisms of Disease".
%D 2016
%R 10.1038/npjamd.2016.19
%X Alzheimer¡¯s disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid ¦Â-peptide (A¦Â) accumulates in the brain. Extracellular vesicles (EVs), including exosomes, are small 50¨C150£¿nm membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient cerebrospinal fluid and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca2+ homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity. EVs contain a relatively low amount of A¦Â but have an increased A¦Â42/ A¦Â40 ratio; the majority of A¦Â is located on the surface of the EVs. Impairment of lysosome function results in increased generation of EVs with elevated A¦Â42 levels. EVs may mediate transcellular spread of pathogenic A¦Â species that impair neuronal Ca2+ handling and mitochondrial function, and may thereby render neurons vulnerable to excitotoxicity
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137253/